The importance of movable genetic elements is becoming clear in an increasing number of prokaryotic and eukaryotic systems. Movable Genetic Elements can cause diverse genetic rearrangements--such as insertions, deletions, substitutions, duplications, amplifications, and inversions. These rearrangements may alter expression of genes. We propose to study the mechanisms by which specific genetic rearrangements occur and affect gene expression in different organisms. In prokaryotes, we will study the mechanism of transposition of bacteriophage Mu DNA in Escherichia coli and the flip-flop of the G segment of Mu DNA. In lower eukaryotes, we will study the mechanism of tansposition of the mating type locus and the flip-flop of the invertible segment of the 2 micron circle in Saccharomyces cerevisiae. In higher eukaryotes, we will study the mechanism of integration of the exogenously added genes into the genome of mammalian cells.